Urinary Trichloroacetic Acid Concentrations Research Articles

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study

BackgroundDisinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. MethodsThis study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. ResultsAfter adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = −1.29 %, 95 % CI: −2.49 %, −0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = −2.49 %, 95 % CI: −4.71 %, −0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. ConclusionUrinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study.

Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. We aimed to explore the associations between HAA exposures and liver injury. We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers. There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage ; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage ; 95% CI: , ). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (). Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study

BackgroundExperimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. ObjectiveThis study aimed to explore the relationships of DBP exposures with blood coagulation parameters. MethodsAmong 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. ResultsElevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). ConclusionHigher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Measurement of haloacetic acids in human urine samples from six megacities of China using a refined detection method

Haloacetic acids (HAAs) are common disinfection by-products in chlorine disinfected water. Humans are extensively exposed to them. However, nationwide biomonitoring data were not available for any country. This study developed a labor-efficient and sensitive method for the detection of urinary HAAs, including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA), and conducted an exposure assessment in a Chinese population. A total of 850 first-morning-void urine samples were collected from adults in six megacities in China: Wuhan (central), Lanzhou (northwest), Chengdu (southwest), Taiyuan (north), Shanghai (east), and Dalian (northeast). Each participant (n = 425) provided a pair of urine samples during the warm (September to October 2018) and cold (December 2018 to January 2019) seasons. The detection method achieved good retention of the target analytes using a Fluoro-Phenyl column and excellent selectivity using in-source fragmentation ions as precursor ions in multiple reaction monitoring. The detection rate of urinary TCAA in Chinese populations was high (78.5%) but varied among different regions (54.0% to 98.0%). DCAA was rarely detected (<10%). The overall median value of specific gravity adjusted TCAA concentrations was 5.70 μg/L in the warm season and 3.87 μg/L in the cold season, respectively. Higher urinary TCAA concentrations were more likely to occur in Wuhan (Yangtze River Basin), urban areas, and during the warm season. The upstream region of the Yangtze River Basin (Chengdu) typically has lower TCAA concentrations. TCAA formation in coastal cities such as Shanghai and Dalian may be impacted by seawater intrusion. Estimated daily intakes of TCAA were lower than its chronic reference dose of 20 μg/kg-bw/day. This detection method can be applied to future biomonitoring of urinary HAAs. More attention should be paid to the highly exposed subgroups when exploring the health effects of long-term TCAA exposure.

Associations between Urinary Concentrations of Disinfection Byproducts and in Vitro Fertilization Outcomes: A Prospective Cohort Study in China.

Experimental studies show that disinfection byproducts (DBPs) can inhibit oocyte maturation, decrease fertilization capacity, and impair embryo development, but human evidence is lacking. We aimed to evaluate the associations between exposure to drinking water DBPs and in vitro fertilization (IVF) outcomes. The study included 1,048 women undergoing assisted reproductive technology (ART) treatment between December 2018 and January 2020 from a prospective cohort study, the Tongji Reproductive and Environmental study in Wuhan, China. Exposure to DBPs was assessed by dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in up to four urine samples, which were collected on the day of both enrollment and oocyte retrieval. Multivariable generalized linear mixed models, accounting for multiple IVF cycles per woman, were applied to evaluate the associations between urinary biomarkers of DBP exposures and IVF outcomes. Stratified analyses were used to explore the potential effect modifiers. The included 1,048 women underwent 1,136 IVF cycles, with 960 (91.6%), 84 (8.0%), and 4 (0.4%) women contributing one cycle, two cycles, and three cycles, respectively. We found that elevated quartiles of urinary DCAA and TCAA concentrations were associated with reduced numbers of total oocytes and metaphase II oocytes and that urinary DCAA concentrations with a lower proportion of best-quality embryos (all p for ). Moreover, elevated quartiles of urinary DCAA concentrations were associated with decreased proportions of successful implantation, clinical pregnancy, and live birth (14%, 15%, and 15% decreases in adjusted means comparing the extreme quartiles, respectively; all p for ). Stratification analyses showed that the inverse associations of urinary TCAA concentrations with multiple IVF outcomes were stronger among women y of age (p for ). Exposure to drinking water DBPs was inversely associated with some IVF outcomes among women undergoing ART treatment. Further study is necessary to confirm our findings. https://doi.org/10.1289/EHP12447.

Associations of Urinary Trichloroacetic Acid Concentrations with Spermatozoa Apoptosis and DNA Damage in a Chinese Population.

Exposure to trichloroacetic acid (TCAA) has been associated with impaired semen quality; however, its association with spermatozoa apoptosis and DNA damage remains unclear. We, therefore, collected single semen and repeated urine samples from male partners of couples attending a reproductive center, which were measured for spermatozoa apoptosis and DNA damage parameters and TCAA concentrations, respectively. Multivariable linear regression models were used to explore the associations between urinary TCAA concentrations and spermatozoa apoptosis (n = 462) and DNA damage parameters (n = 512). After adjusting for potential confounders, positive dose-response relationships were found between urinary TCAA concentrations and percentage of tail DNA (tail%) and tail-distributed moment (TDM) (both p for trend <0.10). Compared with men in the lowest tertile of urinary TCAA concentrations, men in the highest tertile had a greater tail% and TDM of 6.2% (95% CI: 0.7, 12.2%) and 8.9% (95% CI: -1.9, 20.5%), respectively. Urinary TCAA concentrations were unrelated to spermatozoa apoptosis parameters in a dose-response manner. However, urinary TCAA concentrations were positively associated with the percentage of Annexin V+/PI- spermatozoa (apoptotic cells), when urinary TCAA concentrations were modeled as continuous variables. Our results suggest that exposure to TCAA at concentrations in real-world scenarios may be associated with spermatozoa apoptosis and DNA damage.

Associations between drinking water disinfection byproducts and menstrual cycle characteristics: A cross-sectional study among women attending an infertility clinic.

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR=1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend=0.05) and long menstrual cycle (OR=1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend=0.06), as well as prolonged variation in cycle length (β=1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend=0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (β=0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend=0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies.

Increased risk of occupational trichloroethylene hypersensitivity syndrome at exposure levels higher than 15 mg/L of urinary trichloroacetic acid, regardless of whether the patients had the HLA-B*13:01 allele

Occupational trichloroethylene (TCE) exposure can cause hypersensitivity syndrome (TCE-HS). The human leukocyte antigen (HLA)-B*13:01 is reportedly an important allele involved in TCE-HS onset. However, the threshold exposure level causing TCE-HS in relation to HLA-B*13:01 remains unknown. We conducted a case-control study comprising 37 TCE-HS patients and 97 age- and sex-matched TCE-tolerant controls from the Han Chinese population. Urine and blood of patients were collected on the first day of hospitalization, and those of controls were collected at the end of their shifts. Urinary trichloroacetic acid (TCA) was measured as an exposure marker, and end-of-shift levels in the patients were estimated using the biological half-life of 83.7 h. HLA-B genotype was identified using DNA from blood. Crude odds ratios (ORs) for TCE-HS in the groups with urinary TCA concentration >15 mg/L to ≤50 mg/L and of >50 mg/L were 21.9 [95% confidence interval (CI) 4.2–114.1] and 27.6 (6.1–125.8), respectively, when the group with urinary TCA ≤15 mg/L was used as a reference. The frequency of HLA-B*13:01, the most common allele in the patients, was 62.2% (23/37), which was significantly higher than 17.5% (17/97) in the TCE-tolerant controls, with a crude OR of 8.4 (3.1–22.6). The mutually-adjusted ORs for urinary TCA >15 to ≤50 mg/L, >50 mg/L, and for HLA-B*13:01 were 33.4 (4.1–270.8), 34.0 (5.3–217.1), and 11.0 (2.4–50.7), respectively. In conclusion, reduction of TCE exposure to ≤15 mg/L is required for TCE-HS prevention because urinary TCA concentration >15 mg/L showed increased risk of TCE-HS, regardless of whether the patients had the HLA-B*13:01 allele.

Maternal urinary levels of trichloroacetic acid and association with adverse pregnancy outcomes.

The current study aimed to determine the association between trichloroacetic acid (TCAA) levels and adverse pregnancy outcomes among third-trimester pregnant women who were exposed to chlorinated drinking water. A total of 205 pregnant women who participated in the disinfection by-products exposure and adverse pregnancy outcome study in South Africa were randomly asked to participate in this study by providing their morning urine sample voids. Samples were analysed for urinary creatinine and TCAA. Furthermore, participants gave individual data using a structured questionnaire. The mean (median) concentration of creatinine-adjusted urinary TCAA was 2.34 (1.95) μg/g creatinine. Elevated levels of creatinine-adjusted TCAA concentrations showed an increased risk of premature birth, small for gestational age (SGA) and low birth weight. There was no significant statistical correlation observed between creatinine-adjusted TCAA concentrations and the total volume of cold water ingested among the study population. No statistically significant association was observed between creatinine-adjusted urinary TCAA and premature birth, SGA and low birth weight newborns among the study subjects. However, the urinary TCAA concentrations identified in this study suggest potential health risks towards women and foetus. Therefore, further studies are warranted to prevent further adverse pregnancy outcomes.

Genetic damage in young swimmers exposed to pool disinfection by-products

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR = 1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend = 0.05) and long menstrual cycle (OR = 1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend = 0.06), as well as prolonged variation in cycle length (β = 1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend = 0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (β = 0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend = 0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies.

Guidance for the risk assessment of enzyme-containing consumer products

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR = 1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend = 0.05) and long menstrual cycle (OR = 1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend = 0.06), as well as prolonged variation in cycle length (β = 1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend = 0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (β = 0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend = 0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies.

Exposure reconstruction of trichloroethylene among patients with occupational trichloroethylene hypersensitivity syndrome.

Occupational trichloroethylene (TCE) exposure can induce life-threatening generalized dermatitis accompanied by hepatitis: TCE hypersensitivity syndrome (HS). Since the patients’ exposure levels have not been fully clarified, this study estimated end-of-shift urinary concentrations of trichloroacetic acid (TCA) and their lower limit below which the disease occurrence was rare. TCA concentration was measured in 78 TCE HS patients whose urine was collected at admission between 2nd and 14th d after their last shift. Then a linear regression model was used to calculate the mean TCA concentration with 95% confidence interval (95% CI) and 95% prediction interval (95% PI) in the end-of-shift urine. The estimated mean concentration was 83 (95% CI, 49–140) mg/l with 95% PI 9.6–720 mg/l. TCA concentrations were also measured in the end-of-shift urine of 38 healthy workers involved in the same job as were the patients. The geometric mean and its 95% CI were 127 mg/l and 16–984 mg/l, respectively. The exposure levels in HS patients might have thus overlapped with those in workers without HS. Accordingly, it was suggested that HS occurred in the environment where the workers were exposed to the TCE concentration corresponding to the urinary TCA concentration as low as 10 mg/l.

Predictors of Third Trimester Blood Trihalomethanes and Urinary Trichloroacetic Acid Concentrations among Pregnant Women.

Prenatal exposure to disinfection byproducts (DBPs) has been associated with a variety of adverse birth outcomes. However, little is known about predictors of prenatal biomarkers of exposure to DBPs among pregnant women. We aimed to identify predictors of third trimester blood trihalomethanes (THMs) and urinary trichloroacetic acid (TCAA) concentrations, two biomarkers of exposure to DBPs, among pregnant women. Blood samples, urine samples, and questionnaires on individual characteristics and water-use activities were collected from 893 pregnant women in a Chinese cohort study. Maternal blood THM [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA concentrations were measured. We used multivariable linear regression to identify the predictors of third trimester blood THM and creatinine-adjusted urinary TCAA concentrations. The geometric mean of blood TTHM (sum of TCM, BDCM, DBCM, and TBM) and creatinine-adjusted urinary TCAA concentrations were 51.90 ng/L and 9.66 μg/g creatinine, respectively. Study city was the strongest significant predictors of blood THM and creatinine-adjusted urinary TCAA concentrations. Prenatal body mass index (BMI) was associated with decreased blood THM and decreased creatinine-adjusted urinary TCAA concentrations. Age was associated with increased blood Br-THM (sum of BDCM, DBCM, and TBM) concentrations. Intake of boiled water and passive smoking were associated with lower blood THM concentrations. The predictors of blood THM and urinary TCAA concentrations identified in this study provide potential health implications on how to reduce DBP exposure during pregnancy.

Seasonal Variation of Urinary Trichloroacetic Acid (TCAA) Concentrations Measured on Multiple Consecutive Days in a Prospective, Pre-Conception Cohort

Seasonal Variation of Urinary Trichloroacetic Acid (TCAA) Concentrations Measured on Multiple Consecutive Days in a Prospective, Pre-Conception CohortAbstract Number:1826 Kyley Cox*, Christina Porucznik, James VanDerslice, Joseph Stanford, Diana Wilkins, Eric Brozek, David Anderson, and Nicole Bailey Kyley Cox* University of Utah Department of Family and Preventive Medicine, United States, E-mail Address: [email protected] Search for more papers by this author , Christina Porucznik University of Utah Department of Family and Preventive Medicine, United States, E-mail Address: [email protected] Search for more papers by this author , James VanDerslice University of Utah Department of Family and Preventive Medicine, United States, E-mail Address: [email protected] Search for more papers by this author , Joseph Stanford University of Utah Department of Family and Preventive Medicine, United States, E-mail Address: [email protected] Search for more papers by this author , Diana Wilkins University of Utah Center for Human Toxicology, United States, E-mail Address: [email protected] Search for more papers by this author , Eric Brozek University of Utah Center for Human Toxicology, United States, E-mail Address: [email protected] Search for more papers by this author , David Anderson University of Utah Center for Human Toxicology, United States, E-mail Address: [email protected] Search for more papers by this author , and Nicole Bailey University of Utah Department of Family and Preventive Medicine, United States, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: Control of bacterial contamination of drinking water by disinfectants leads to the production of disinfection-by-products (DBPs). TCAA is the second most prevalent haloacetic acid in chlorinated water. Urinary TCAA is a validated biomarker of TCAA exposure by ingestion of chlorinated drinking water. Objective: Evaluate variation of urinary TCAA concentrations by season.Methods: A prospective, pre-conception cohort of couples (women 18–35, men 18–40) was recruited in Utah beginning in early 2012. Recruitment is ongoing. Women observed cervical mucus to identify the fertile window. Participants collected first-morning urine samples beginning at the onset of the fertile window, after which men discontinued collecting but women collected for the remainder of the cycle. TCAA was measured in each urine sample using quantitative GC-MS. Geometric means (GM) with 95% confidence intervals (CI) were calculated for each season using STATA ver. 12. Seasons were defined as follows: spring (Mar – May); summer (June – Aug); fall (Sept – Nov); winter (Dec – Feb).Results: The GM for all specimens (n=1521) was 2.42 ng/mL (95% CI 2.32, 2.53). The highest concentrations were observed in specimens collected during spring months (n=212, GM 3.04 ng/mL, 95% CI 2.76, 3.35), followed by fall (n=428, GM 2.69 ng/mL, 95% CI 2.47, 2.93), and summer (n=519, GM 2.53 ng/mL, 95% CI 2.37, 2.69). These levels were significantly higher than the levels observed during winter (n=362, GM 1.76 ng/mL, 95% CI, 1.61, 1.93). Men had slightly higher levels than women (GM 2.64 vs. 2.36 ng/mL) but the difference was not statistically significant.Conclusions: These preliminary findings suggest that TCAA exposures vary seasonally in a pattern similar to the levels of disinfection byproducts in tap water.

Predictors of urinary trichloroacetic acid and baseline blood trihalomethanes concentrations among men in China

Urinary trichloroacetic acid (TCAA) and baseline blood trihalomethanes (THMs) have been measured as biomarkers of exposure to drinking water disinfection by-products (DBPs) that have been associated with increased risk of cancers and adverse reproductive outcomes. This study aimed to identify predictors of urinary TCAA and baseline blood THMs among men in China. Urine samples, blood samples, and information on socio-demographic factors and water-use activities were collected from 2216 men who participated in a cross-sectional study of exposure to drinking water DBPs and reproductive health during 2011 to 2012. Urinary TCAA and baseline blood THMs including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were analyzed. Multivariable linear regression was used to evaluate predictors of urinary TCAA and baseline blood THM concentrations. Tap water consumption was significantly associated with creatinine-adjusted urinary TCAA concentration (β=0.23μg/g creatinine per log10 unit; 95% CI: 0.12, 0.35). Men with surface water source had 0.13 (95% CI: 0.00, 0.27) higher mean creatinine-adjusted urinary TCAA concentrations than those with ground water source. Smoking was associated with lower concentration of creatinine-adjusted urinary TCAA. Age was significantly associated with baseline blood Br-THM (sum of BDCM, DBCM, and TBM) concentration (β=0.01ng/L per unit; 95% CI: 0.00, 0.02). Increased household income was associated with decreased concentrations of baseline blood BDCM and Br-THMs. Our results suggest that tap water consumption, water source, smoking, age, and household income as the primary determinants of exposure to drinking water DBPs should be considered in exposure assessment.

Drinking-Water Disinfection By-products and Semen Quality: A Cross-Sectional Study in China

Background: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent.Objective: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population.Methods: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples.Results: The mean (median) urinary TCAA concentration was 9.58 (7.97) μg/L (interquartile range, 6.01–10.96 μg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility.Conclusion: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.Citation: Zeng Q, Wang YX, Xie SH, Xu L, Chen YZ, Li M, Yue J, Li YF, Liu AL, Lu WQ. 2014. Drinking-water disinfection by-products and semen quality: a cross-sectional study in China. Environ Health Perspect 122:741–746; http://dx.doi.org/10.1289/ehp.1307067

Trichloroacetic acid in urine as biological exposure equivalent for low exposure concentrations of trichloroethene

A urinary trichloroacetic acid (TCA) concentration of 100mg/l at the end of the last work shift (8h/day, 5days/week) of the week has been established in workers as exposure equivalent for the carcinogenic substance trichloroethene (EKA for TRI) at an exposure concentration of 50ppm TRI. Due to the continuous reduction of atmospheric TRI concentrations during the last years, the quantitative relation given by the EKA for TRI is revised for exposures to low TRI concentrations. A physiological two-compartment model is presented by which the urinary TCA concentrations are calculated that result from inhaled TRI in humans. The model contains one compartment for trichloroethanol (TCE) and one for TCA. Inhaled TRI is metabolized to TCA and to TCE. The latter is in part further oxidized to TCA. Urinary elimination of TCA is modeled to obey first order kinetics. All required model parameters were taken form the literature. In order to evaluate the model performance on the urinary TCA excretion at low exposure concentrations, predicted urinary TCA concentrations were compared with data obtained in two volunteer studies and in one field study. The model was evaluated at exposure concentrations as low as 12.5ppm TRI. It is demonstrated that the correlation described by the hitherto used EKA for TRI is also valid at low TRI concentrations. For TRI exposure concentrations of 0.6 and 6ppm, the resulting urinary TCA concentrations at the end of the last work shift of a week are predicted to be 1.2 and 12mg/l, respectively.

Trichloroethylene Causes Generalized Hypersensitivity Skin Disorders Complicated by Hepatitis

Idiosyncratic generalized skin disorders complicated by hepatitis, which resemble severe drug hypersensitivities, occur sporadically in workers exposed to trichloroethylene (TCE) in China. However, it has been a matter of controversy whether the solvent itself, not its impurities or stabilizers, can cause hypersensitivity reactions or not. This study aimed to characterize the exposure of hospitalized patients and their healthy colleagues. TCE metabolites were measured in urine of 19 hospitalized patients suffering from the disorders. To assess the exposure of patients' healthy colleagues, on-site surveys were conducted in 6 factories where the disorders occurred and in 2 control factories without such occurrences despite TCE use. Urinalysis of the patients detected trichloroacetic acid (TCA) in all of them. Its average concentration in the end-of-shift urine was estimated to be 206 mg/l. On-site survey of healthy exposed workers revealed that the maximum urinary TCA concentrations and the maximum time-weighted average concentrations of personal TCE exposure were 318-1,617 mg/l and 164-2,330 mg/m(3), respectively. There was no common impurity in TCE used in the factories. These results suggested that TCE itself caused the skin hypersensitivity disorders, and that the disorders occurred in factories where TCE metabolites could be extensively accumulated, possibly due to long working hours. Since the lowest TCA concentration in the end-of-shift urine of the patients was estimated to be 72-80 mg/l, it is recommended to control TCE exposure to keep the urinary TCA concentration below 50 mg/l to reduce the disease risk.

VALIDATING URINARY TRICHLOROACETIC ACID AS A BIOMARKER OF EXPOSURE FOR DISINFECTION BY-PRODUCTS IN DRINKING WATER

ISEE-114 Introduction: Epidemiologic evidence of disinfection by-products (DBPs) causing adverse human health effects needs improved assessment of individual drinking water exposure to DBPs. Development of a feasible biomarker offers an approach to this need. Trichloroacetic acid (TCAA) in urine was confirmed to have sufficiently long retention (urinary excretion half lives from 2 to s6 days) in two previous human exposure pilot trials (ten participants in Adelaide, Australia and five participants in Edmonton, Canada) to make urinary TCAA a promising candidate as a biomarker. Aim: The current study was to validate urinary TCAA as a biomarker of non-volatile DBP exposure via drinking water. Methods: Between May 2003 and April 2004, fifty-two healthy women of reproductive age were recruited to participate in this study. Following an initial telephone interview, eligible volunteers were selected to obtain demographic data, patterns of food, beverage and water consumption, and to set up schedules for water delivery and blood and urine sample collections. All participants were randomly stratified into five sub-groups. Each exposure level was assigned a different exposure status. Each participant ingested supplied municipal tap water, diluted to a known degree with TCAA-free water, every day for a 15-day period of time, and provided urine samples on the 1st, 2nd, 8th, 13th, 14th, 15th, and 16th day of the exposure period. Some provided blood samples on the 1st, 8th, 14th, and 15th day. Results: The means of background TCAA levels were 6.6 mg/l for urinary TCAA concentration, 5.2 mg/g cr for creatinine-adjusted TCAA, 6.1 mg/d for amount of urinary TCAA excretion, and 13 mg/l for blood TCAA concentration. There were good correlations between urinary TCAA excretion and TCAA ingestion (R values: 0.72 – 0.80) and between blood TCAA concentration and TCAA ingestion (R = 0.74). Variation in volume of tap water intake affected the amount of TCAA intake in the majority of individuals. The correction of urinary excretion to urinary creatinine improved the result of intra-individual variability to a limited extent. On average, 37% of amount of ingested TCAA was measured in urine samples. The intra-individual variability of urinary TCAA excretion was relatively small after Exposure Day 7 (intra-class correlation coefficient >0.90). Discussion: The value of TCAA as a biomarker of exposure for DBPs in drinking water will be characterized.

Biological monitoring of kidney function among workers occupationally exposed to trichloroethylene

Aims: To investigate the nephrotoxic potential of trichloroethylene in a currently exposed population using sensitive urinary markers of kidney toxicity. Methods: Renal dysfunction was monitored in a cross-sectional study of...